A specific subset of CD4+ T cells, termed TH17 cells (T helper 17 cells), has been implicated in the pathogenesis of a number of inflammatory/autoimmune diseases, including those neuroinflammatory conditions involving CNS infiltration of T cells, such as multiple sclerosis (MS).
MS is a chronic inflammatory/autoimmune demyelinating disease of the central nervous system (CNS) mostly affecting young adults between 20 and 40 years old, characterized by inflammatory attacks to the central nervous system. Clinically, the disease ranges from relapsing-remitting to chronic progressive in nature. To date, MS is the first cause of non-traumatic disability in young people. Pathologically, the disease is characterized by the presence of T lymphocytes, immunoglobulins, activated macrophages and pro-inflammatory cytokines (i.e., IL-12, IL-23, IL-1 and IL-6) within focal CNS lesions, causing myelin loss, oligodendrocyte death and axonal damage.
There are few treatment regimens currently used in MS. Corticosteroids have anti-inflammatory and immunosuppressive effects. However, the responsiveness to corticosteroids declines over time, and extended use may lead to adrenal suppression, cardiovascular collapse and arrhythmias. (C. F. Lacy et al., Drug information handbook 8th Edition, 2001, pp. 549-551).
Interferon-β has been used as a therapy for patients with active Relapsing/Remitting Multiple Sclerosis (RRMS) since the 1980's. Recombinant IFN is available in 3 drugs: IFNβ-1b (Betaseron™) and two IFN-β-Ia preparations (Avonex™ and Rebif™). These drugs reduce the rate of clinical relapse. However, neutralizing antibodies develop against these drugs rendering them ineffective with time. Also, flu-like symptoms are a prominent side effect early on in the treatment.
Glatiramer acetate (Copaxone™) is a synthetic co-polymer of tyrosine, glutamate, alanine and lysine, thought to mimic myelin basic protein (MBP) and thus, block T cell recognition of MBP (Karin N. et al., (1994) J Exp Med. 180(6): 2227-37). However, treatment with this drug may cause cardiovascular problems such as chest pain, flushing and tachycardia, and respiratory problems such as dyspnea (C. F. Lacy et al., supra).
Another drug that has been approved for the use in RRMS and secondary progressive MS is mitoxantrone, which however has long-term side effects causing cardiac toxicity.
Therefore, while there are a few moderately effective treatments for RRMS and secondary progressive MS, problems still exist in treating MS, and there are still no proven treatments, for example, for primary progressive MS.
Furthermore, there is currently no monoclonal antibodies directed against DICAM that may be used for flow cytometry applications and/or that may be used to block DICAM activity.
Thus, there is a need in the art to identify and use molecules that are involved in the infiltration of inflammatory immune cells such as TH17 cells into inflamed tissues. These molecules can be targets to design therapeutic agents for inflammatory/autoimmune conditions, such as MS and Parkinson's disease (PD), as well as other TH17-mediated inflammatory conditions not associated with the central nervous system. There is also a need to identify novel antibodies that can bind to and/or are capable of reducing, interfering, or otherwise blocking the interaction between DICAM expressed on the surface of TH17 and its identified ligand.
There is also a continued need for novel reagents and methods for detecting DICAM.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.